Continuous-fiber reinforced biocomposite medical implants

ABSTRACT

A medical implant comprising a plurality of layers, each layer comprising a polymer and a plurality of uni-directionally aligned continuous reinforcement fibers.

BACKGROUND

Permanent Orthopedic Implant Materials

Medical implants can be manufactured from metals, alloys, ceramics orboth degradable and stable composites. In load-bearing, orthopedicapplications that require high strength, usually stainless steel ortitanium alloys are used. Metal implants have a long history ofsuccessful use in orthopedic surgery but also carry many risks forcomplications. Although these materials are inert, they are also used insituations in which the need for the implant is only temporary, like infracture fixation. In the case of metal rods and plates for fracturefixation, a second surgery for device removal may be recommended aboutone year after confirmation of osseous union. Implant removal causesadditional risk and added morbidity for the patient, occupies theavailability of clinics, and increases the overall procedure costs. Ifthe device is not removed, it may cause remodeling of the bone. Suchremodeling may in turn weaken the bone due to stress shielding orinflammation of the host tissue. The stress shielding can occur due tothe high stiffness (modulus) and strength of the metals compared to thestiffness and strength of the cortical bone, so that the metal stressesthe bone, which can result in periprosthetic fractures or loss of bonestrength.

Examples of load-bearing medical implants that have traditionally beenconstructed of metal alloys include bone plates, rods, screws, tacks,nails, clamps, and pins for the fixation of bone fractures and/orosteotomies to immobilize the bone fragments for healing. Other examplesinclude cervical wedges, lumbar cages and plates and screws forvertebral fusion and other operations in spinal surgery.

Biostable polymers and their composites e.g. based on polymethacrylate(PMMA), ultra high molecular weight polyethylene (UHMWPE),polytetrafluoroethylene (PTFE), polyetheretherketone (PEEK),polysiloxane and acrylic polymers have also been used to manufacturemedical implants. These materials are not biodegradable or bioresorbableand therefore face many of the same limitations as the metals when usedfor medical implant applications, for example they may require a secondsurgery for replacing or removing the implant at some point of thelifetime of the implant. Furthermore, these materials are weaker (lessstrong and stiff) than metal such that they are more susceptible tomechanical failure, particularly after repeated dynamic loading (i.e.through material fatigue or creep).

Existing Degradable Polymer Medical Implants

Resorbable polymers have been used to develop resorbable implants, whichcan also be referred to as absorbable, bioabsorbable, or biodegradableimplants. The advantage of using biocompatible, resorbable polymers isthat the polymers, and thus the implant, resorb in the body and releasenon-toxic degradation products that are metabolized by the metabolicsystem. Polymers, including polylactic and polyglycolic acids andpolydioxanone, are resorbable biocompatible materials that are currentlyused as orthopedic plates, rods, anchors, pins or screws for non-loadbearing medical implant applications, such as craniofacial applications.These medical implant materials offer the advantage of eventualresorption, eliminating the need for later removal, while allowingstress transfer to the remodeling fracture. However, currentbioabsorbable materials and implants do not have mechanical propertiesto match metallic implants. The mechanical strength and modulus(approximately 3-5 GPa) of non-reinforced resorbable polymers, isinsufficient to support fractured cortical bone, which has an elasticmodulus in the range of approximately 15-20 GPa (Snyder S M, et al.measured the bending modulus of human tibial bone to be about 17.5 GPaSnyder S M Schneider E, Journal of Orthopedic Research, Vol. 9, 1991,pp. 422-431). Therefore, the indications of existing medical implantsconstructed from resorbable polymers are limited and their fixationusually requires protection from motion or significant loading. Thesedevices are only a consideration when fixation of low stress areas isneeded (i.e. non-load bearing applications) such as in pediatricpatients or in medial malleolar fractures, syndesmotic fixation,maxillofacial, or osteochondral fractures in adults.

Reinforced Degradable Polymer Materials

Recently, reinforced polymer materials with improved strength andstiffness (modulus) have been introduced. These biodegradable compositescomprise polymers reinforced by fillers, usually in fiber form. Incomposite materials, usually a relatively flexible matrix (i.e. apolymer) is combined with a stiff and strong reinforcement material toenhance the mechanical properties of the composite matrix. For example,biodegradable glass or mineral material can be used to improve thestiffness and strength of a biodegradable polymer matrix. In the priorart, several attempts to produce such a composite were reported wherebioactive glass particles, hydroxyapatite powder, or short glass fiberswere used to enhance the properties of a biodegradable polymer. In mostcases, the strength and stiffness of these composites is lower thancortical bone or becomes lower than cortical bone following rapiddegradation in a physiological environment. Therefore, the majority ofthese composite materials are not appropriate for use in load-bearingmedical implant applications. However, biodegradable composites withstrength and stiffness equivalent to or greater than cortical bone haverecently been reported, for example a biodegradable composite comprisinga biodegradable polymer and 20-70 vol % glass fibers (WO2010128039 A1).Other composite material implants, for example formed of polymerreinforced with fibers, are disclosed in U.S. Pat. Nos. 4,750,905,5,181,930, 5,397,358, 5,009,664, 5,064,439, 4,978,360, 7,419,714, thedisclosures of which are incorporated herein by reference

Degradation Mechanism of Reinforced Dearadable Polymer Materials

When biodegradable composites are used for load-bearing medical implantapplications, such as to fixate bone fractures, the mechanicalproperties of the medical implant must be retained for an extendedperiod. Degradation of the composite will result in premature loss ofimplant strength or stiffness and can lead to implant function failure,such as insufficient fixation of bone segments resulting in improperbone healing.

Unfortunately, biodegradable composites will begin to hydrolyticallydegrade once they come into contact with body fluid. This degradationcan be a result of degradation of the biodegradable polymer, reinforcingfiller, or both. Such degradation in an aqueous environment, such as thephysiological environment, can particularly result in a sharp drop-offof mechanical strength and stiffness in certain reinforced polymermaterials that are reinforced by inorganic compounds. Where theabsorbable polymer matrix is organic material, and the fillers areinorganic compounds, the adhesion between the absorbable polymer matrixand the filler may be reduced by degradation of either the polymer orfiller in the aqueous environment and become rapidly reduced such thatthe initial mechanical properties of the reinforced polymer drop-offrapidly and become less than desirable for adequate load-bearingperformance. Aside from the degradation of the polymer and fillerseparately, poor polymer to reinforcement interface interaction andadhesion can result in early failure at the interface in a aqueousenvironment, thereby resulting in sharp mechanical property drop off asthe reinforcement detaches from the polymer and the reinforcing effectof the filler is lost.

Tormälä et al. (WO 2006/114483) described a composite materialcontaining two reinforcing fibers, one polymeric and one ceramic, in apolymer matrix and reported good initial mechanical results (bendingstrength of 420+/−39 MPa and bending modulus of 21.5 GPa) equivalent tothe properties of cortical bone. However, the prior art teaches thatbioabsorbable composites reinforced with absorbable glass fibers, have ahigh initial bending modulus but that they rapidly lose their strengthand modulus in vitro.

While improved interfacial bonding (such as covalent bonding) betweenthe polymer and reinforcement can significantly prolong reinforcedbioabsorbable polymer mechanical property retention in an aqueousenvironment (WO2010128039 A1), continued hydrolysis of the polymer,reinforcement, or interface between the two will result in loss ofmechanical properties over time. Since osseous union may take severalmonths or longer, even the prolonged mechanical property degradationprofile in covalently bonded reinforced bioabsorbable polymers may beinsufficient for optimal function of medical implants used forload-bearing orthopedic applications.

An example of strength loss in a reinforced degradable polymer implantis described with regard to self-reinforced poly-L-lactic acid (Majola Aet al., Journal of Materials Science Materials in Medicine, Vol. 3,1992, pp. 43-47). There, the strength and strength retention ofself-reinforced poly-L-lactic acid (SR-PLLA) composite rods wereevaluated after intramedullary and subcutaneous implantation in rabbits.The initial bending strength of the SR-PLLA rods was 250-271 MPa. Afterintramedullary and subcutaneous implantation of 12 weeks the bendingstrength of the SR-PLLA implants was 100 MPa.

Co- and terpolyesters of PLA, PGA and PCL are of interest in thetailoring of the optimal polymer for resorbable composite material formedical devices. The choice of monomer ratio and molecular weightsignificantly affects the strength elasticity, modulus, thermalproperties, degradation rate and melt viscosity of resorbable compositematerials and all of these polymers are known to be degradable inaqueous conditions, both in vitro and in vivo. Two stages have beenidentified in the degradation process: First, degradation proceeds byrandom hydrolytic chain scission of the ester linkages which decreasesthe molecular weight of the polymers. In the second stage measurableweight loss in addition to chain scission is observed. The mechanicalproperties are mainly lost or at least a remarkable drop will be seen inthem at the point where weight loss starts. Degradation rate of thesepolymers is different depending on the polymer structure: crystallinity,molecular weight, glass transition temperature, block length,racemization and chain architecture. (Middleton J C, Tipton A I,Biomaterials 21, 2000, 2335-2346)

SUMMARY OF THE INVENTION

There is a great need for a reinforced bioabsorbable polymer materialexhibiting improved mechanical properties for use in load-bearingmedical implant applications, such as structural fixation forload-bearing purposes, where the high strength and stiffness of theimplant are retained at a level equivalent to or exceeding cortical bonefor a period at least as long as the maximum bone healing time.

The construction of biocomposite fiber-reinforced materials with therequisite high strength and stiffness is known in the art to be adifficult problem, which so far has not been provided with an adequatesolution.

Specifically within such fiber-reinforced composites, achieving the highstrengths and stiffness required for many medical implant applicationscan require the use of continuous-fiber reinforcement rather than shortor long fiber reinforcement. This creates a significant difference fromthe implant structures, architectures, designs, and productiontechniques that have been previously used with medical implants producedfrom polymers or composites comprising short or long fiber reinforcedpolymers. Those implants are most commonly produced using injectionmolding, or occasionally 3-D printing, production techniques. Theproduction of these implants generally involves homogeneity of thematerial throughout the implant and the finished implant is thencomprised of predominantly isotropic material. However, with continuousfiber-reinforcement, the fibers must be carefully aligned such that eachfiber or bundle of fibers runs along a path within the compositematerial such that they will provide reinforcement along specific axeswithin the implant to provide stress resistance where it is most needed.

Unlike with bulk materials, the properties of parts made from compositematerials are highly dependent on the internal structure of the part.This is a well-established principle in the design of parts fromcomposite materials where the mechanical properties of fiber-reinforcedcomposite materials are known to be dependent on the angles andorientations of the fibers within the composite parts.

The vast majority of prior composite material part design focusedexclusively on the mechanical properties of the parts. However, theseparts were permanent parts and not degradable or absorbable. Therefore,no attention had to be given to the mechanisms of degradation orabsorption of the composite materials within the part. Even previousorthopedic implants comprised of composite materials have largelyadhered to these same classical composite material design principles.

However, the herein invention relates to medical implants comprised of anew class of composite materials that are biocompatible and in manycases are bioabsorbable. The design challenges in creating medicalimplants with these materials involve consideration of many more aspectsand parameters than just the mechanical properties that have previouslybeen considered with composite material parts.

Furthermore, with regard to bioabsorbable continuous fiber-reinforcedcomposite implants, the degradation profile of the composite materialwithin the implant must also be taken into consideration in ensuringthat the continuous fibers will provide strength and stiffnessreinforcement both initially at the initial time of device implantationand also over the course of its functional period within the body.

Mechanical properties that are critical to the performance of medicalimplants in the herein invention include: flexural, tensional, shear,compressional, and torsional strength and stiffness (modulus). In thesebioabsorbable medical implants, these properties are critical both attime zero (i.e. in the implant following production) and following aperiod of implantation in the body. As with previously described partsmade from fiber-reinforced composite material, the mechanical propertiesat time zero are dependent on the alignment and orientation of fiberswithin the part. However, retaining a large percentage of the mechanicalproperties following implantation in the body (or simulatedimplantation) requires additional and different considerations.

As will be described in more detail below, such considerations for themedical implant design can include the following parameters:compositions, component ratios, fiber diameters, fiber distribution,fiber length, fiber alignments and orientations, etc.

These parameters can impact several additional aspects and properties ofthe herein described medical implant performance:

1. Material degradation rate (degradation products, local pH and ionlevels during degradation)

2. Surface properties that affect interface of implant with surroundinglocal tissue

3. Biological effects such as anti-microbial or osteoconductiveproperties

4. Response to sterilization processes (such as ethylene oxide gas,gamma or E-beam radiation)

The present invention provides a solution to these problems byproviding, in at least some embodiments, implant compositions fromcontinuous-fiber reinforced biocompatible composite materials that are asignificant step forward from previous implants in that they can achievesustainably high, load bearing strengths and stiffness. Additionally,many embodiments of the present invention additionally facilitate thesehigh strength levels with efficient implants of low volume. Furthermore,the biocomposite materials described herein are also optionally andpreferably bioabsorbable.

The present invention therefore overcomes the limitations of previousapproaches and provides medical implants comprising (optionallybiodegradable) biocomposite compositions featuring continuousfiber-reinforcement that retain their mechanical strength and stiffnessfor an extended period.

According to at least some embodiments, there is provided a medicalimplant comprising a plurality of biocomposite layers, said layerscomprising a polymer, which is optionally biodegradable, and a pluralityof uni-directionally aligned continuous reinforcement fibers. Optionallyand preferably, the biodegradable polymer is embodied in a biodegradablecomposite. Also optionally and preferably, the fibers are embedded in apolymer matrix comprising one or more bioabsorbable polymers.

According to at least some embodiments, the composite layers are eachcomprised of one or more composite tapes, said tape comprising apolymer, which is optionally biodegradable, and a plurality ofuni-directionally aligned continuous reinforcement fibers. Optionallyand preferably, the biodegradable polymer is embodied in a biodegradablecomposite. Also optionally and preferably, the fibers are embedded in apolymer matrix comprising one or more bioabsorbable polymers.

Optionally and preferably, the fiber-reinforced biodegradable compositewithin the implant has a flexural modulus exceeding 10 GPa and flexuralstrength exceeding 100 MPa.

Preferably, the fiber-reinforced biodegradable composite within theimplant has flexural strength in range of 400-800 MPa, more preferably650-800 MPa. Elastic modulus in range of 10-27 GPa. More preferably16-27 GPa.

Preferably, the fiber-reinforced composite within the implant hasstrength retention of Elastic Modulus above 10 GPa after 8 weeksimplantation and flexural strength above 150 MPa after 8 weeks.

The term “biodegradable” as used herein also refers to materials thatare resorbable, bioabsorbable or absorbable in the body.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1: Scanning Electron Microscope (SEM) image using a Back-ScatteredElectrons (BSE) detector of a cross section of a 6 mm pin with 50% fibercontent by weight, such as those described in Example 1. Magnificationof this image is 2,500×. This image shows a magnification of the crosssection of reinforcing mineral fibers 102 embedded within bioabsorbablepolymer matrix 104. The fiber diameter is indicated within the image106.

FIG. 2: Scanning Electron Microscope (SEM) image using a Back-ScatteredElectrons (BSE) detector of a cross section of a 6 mm pin with 50% fibercontent by weight, such as those described in Example 1. Magnificationof this image is 2,500×. This image shows a magnification of the crosssection of reinforcing mineral fibers embedded within bioabsorbablepolymer matrix. The distance between adjacent fibers is indicated by202.

FIG. 3: Scanning Electron Microscope (SEM) image using a Back-ScatteredElectrons (BSE) detector of a cross section of a 6 mm pin with 50% fibercontent by weight, such as those described in Example 1. Magnificationof this image is 500×. This image shows a magnification of the crosssection of reinforcing mineral fibers embedded within bioabsorbablepolymer matrix. Each layer 306 308 310 is comprised of reinforcementfibers 304 and is of a certain thickness 302.

FIG. 4: Scanning Electron Microscope (SEM) image using a Back-ScatteredElectrons (BSE) detector of a cross section of a 6 mm pin with 50% fibercontent by weight, such as those described in Example 1. Magnificationof this image is 150×. This image shows a magnification of the crosssection of reinforcing mineral fibers embedded within bioabsorbablepolymer matrix.

FIG. 5: Scanning Electron Microscope (SEM) image using a Back-ScatteredElectrons (BSE) detector of a cross section of a 6 mm pin with 50% fibercontent by weight, such as those described in Example 1. Magnificationof this image is 500×. This image shows a magnification of the crosssection of reinforcing mineral fibers embedded within bioabsorbablepolymer matrix. Each layer is separated by an area of bioabsorbablepolymer matrix 502.

FIG. 6: Scanning Electron Microscope (SEM) image using a Back-ScatteredElectrons (BSE) detector of a cross section of a 6 mm pin with 70% fibercontent by weight, such as those described in Example 1. Magnificationof this image is 500×. This image shows a magnification of the crosssection of reinforcing mineral fibers embedded within bioabsorbablepolymer matrix. The distance between adjacent fibers is indicated.

FIG. 7: Scanning Electron Microscope (SEM) image using a Back-ScatteredElectrons (BSE) detector of a cross section of a 6 mm pin with 70% fibercontent by weight, such as those described in Example 1. Magnificationof this image is 500×. This image shows a magnification of the crosssection of reinforcing mineral fibers embedded within bioabsorbablepolymer matrix.

FIG. 8: Scanning Electron Microscope (SEM) image using a secondaryelectron detector of Au sputtered cross section of a 2 mm pin with 50%fiber content by weight, such as those described in Example 2.Magnification of this image is 2,000×. This image shows a magnificationof the cross section of reinforcing mineral fibers embedded withinbioabsorbable polymer matrix. The fiber diameter is indicated within theimage.

FIG. 9: Scanning Electron Microscope (SEM) image using a secondaryelectron detector of Au sputtered cross section of a 2 mm pin with 50%fiber content by weight, such as those described in Example 2.Magnification of this image is 2,000×. This image shows a magnificationof the cross section of reinforcing mineral fibers embedded withinbioabsorbable polymer matrix. The distance between adjacent fibers isindicated.

FIG. 10: Scanning Electron Microscope (SEM) image using a secondaryelectron detector of Au sputtered cross section of a 2 mm pin with 50%fiber content by weight, such as those described in Example 2.Magnification of this image is 1,000×. This image shows a magnificationof the cross section of reinforcing mineral fibers embedded withinbioabsorbable polymer matrix.

FIG. 11: Scanning Electron Microscope (SEM) image using a secondaryelectron detector of Au sputtered cross section of a 2 mm pin with 50%fiber content by weight, such as those described in Example 2.Magnification of this image is 5,000×. This image shows a magnificationof the cross section of reinforcing mineral fibers 1102 embedded withinbioabsorbable polymer matrix 1104.

FIG. 12: Scanning Electron Microscope (SEM) image using a secondaryelectron detector of Au Sputtered cross section of a 2 mm pin with 50%fiber content by weight, such as those described in Example 2.Magnification of this image is 1,000×. This image shows a magnificationof the cross section of reinforcing mineral fibers embedded withinbioabsorbable polymer matrix. Each layer is separated by an area ofbioabsorbable polymer matrix.

FIG. 13: Scanning Electron Microscope (SEM) image using a secondaryelectron detector of Au Sputtered cross section of a 2 mm cannulated pinwith 50% fiber content by weight, such as those described in Example 2.Magnification of this image is 1,000×. This image shows a magnificationof the cross section of reinforcing mineral fibers embedded withinbioabsorbable polymer matrix. The fiber diameter is indicated within theimage.

FIG. 14: Scanning Electron Microscope (SEM) image using a secondaryelectron detector of Au Sputtered cross section of a 2 mm cannulated pinwith 50% fiber content by weight, such as those described in Example 2.Magnification of this image is 1,000×. This image shows a magnificationof the cross section of reinforcing mineral fibers embedded withinbioabsorbable polymer matrix. The distance between adjacent fibers isindicated.

FIG. 15: Scanning Electron Microscope (SEM) image using a secondaryelectron detector of Au sputtered cross section of a 2 mm cannulated pinwith 50% fiber content by weight, such as those described in Example 2.Magnification of this image is 1,000×. This image shows a magnificationof the cross section of reinforcing mineral fibers embedded withinbioabsorbable polymer matrix.

FIG. 16: Scanning Electron Microscope (SEM) image using a secondaryelectron detector of Au Sputtered cross section of a 2 mm cannulated pinwith 50% fiber content by weight, such as those described in Example 2.Magnification of this image is 1,000×. This image shows a magnificationof the cross section of reinforcing mineral fibers embedded withinbioabsorbable polymer matrix. Each layer is separated by an area ofbioabsorbable polymer matrix.

FIG. 17: Scanning Electron Microscope (SEM) image using a Back-ScatteredElectrons (BSE) detector of a cross section of a 2 mm plate with 50%fiber content by weight, such as those described in Example 3.Magnification of this image is 1250×. This image shows a magnificationof the cross section of reinforcing mineral fibers embedded withinbioabsorbable polymer matrix. The fiber diameter is indicated within theimage.

FIG. 18: Scanning Electron Microscope (SEM) image using a Back-ScatteredElectrons (BSE) detector of a cross section of a 2 mm plate with 50%fiber content by weight, such as those described in Example 3.Magnification of this image is 1250×. This image shows a magnificationof the cross section of reinforcing mineral fibers embedded withinbioabsorbable polymer matrix. The distance between adjacent fibers isindicated.

FIG. 19: Scanning Electron Microscope (SEM) image using a Back-ScatteredElectrons (BSE) detector of a cross section of a 2 mm plate with 70%fiber content by weight, such as those described in Example 3.Magnification of this image is 250×. This image shows a magnification ofthe cross section of reinforcing mineral fibers embedded withinbioabsorbable polymer matrix. Each layer 1902, 1904 is comprised offibers. The distance between adjacent fibers is indicated.

FIG. 20: Scanning Electron Microscope (SEM) image using a Back-ScatteredElectrons (BSE) detector of a cross section of a 2 mm plate with 70%fiber content by weight, such as those described in Example 3.Magnification of this image is 250×. This image shows a magnification ofthe cross section of reinforcing mineral fibers embedded withinbioabsorbable polymer matrix.

FIG. 21: Scanning Electron Microscope (SEM) image using a Back-ScatteredElectrons (BSE) detector of a cross section of a 2 mm plate with 70%fiber content by weight, such as those described in Example 3.Magnification of this image is 500×. This image shows a magnification ofthe cross section of reinforcing mineral fibers embedded withinbioabsorbable polymer matrix. Each layer is separated by an area ofbioabsorbable polymer matrix.

FIG. 22: Scanning Electron Microscope (SEM) image using a secondaryelectron detector of Au sputtered cross section of a 2 mm pin with 50%fiber content by weight, such as those described in Example 2.Magnification of this image is 300×. This image shows a magnification ofthe longitudinal axis of reinforcing mineral fibers 2202.

FIG. 23: Scanning Electron Microscope (SEM) image using a secondaryelectron detector of Au sputtered cross section of a 2 mm cannulated pinwith 50% fiber content by weight, such as those described in Example 2.Magnification of this image is 250×. This image shows a magnification ofthe cannulated portion and the continuous, reinforcing mineral fibers.The tangential angle 2302 is defined as the deviation from the directionof the curve at a fixed starting point, where the fixed starting pointis the point where the fiber touches or is closest to coming intocontact with the center of the cross-sectional circular area.

FIG. 24: Scanning Electron Microscope (SEM) image using a secondaryelectron detector of Au sputtered cross section of a 6 mm pin with 50%fiber content by weight, such as those described in Example 1.Magnification of this image is 500×. This image shows a magnification ofthe cross section of reinforcing mineral fibers, bundled tightlytogether in groups 2402 embedded within bioabsorbable polymer matrix.

FIG. 25: Scanning Electron Microscope (SEM) image using a secondaryelectron detector of Au sputtered cross section of a 2 mm cannulated pinwith 50% fiber content by weight, such as those described in Example 2.Magnification of this image is 500×. This image shows a magnification ofthe cross section of reinforcing mineral fibers surrounding the innercannulation of the pin 2502.

FIG. 26: Scanning Electron Microscope (SEM) image using a secondaryelectron detector of Au sputtered cross section of a 2 mm cannulated pinwith 50% fiber content by weight, such as those described in Example 2.Magnification of this image is 1000×. This image shows a magnificationof the cross section of reinforcing mineral fibers, embedded withinbioabsorbable polymer matrix layers in alternating 0° and 45°orientation.

FIG. 27: Scanning Electron Microscope (SEM) image using a secondaryelectron detector of Au sputtered cross section of a 6 mm pin with 85%fiber content by weight, such as those described in Example 1.Magnification 160×. This image shows a magnification of the crosssection of reinforcing mineral fibers, embedded within layers 2702 inalternating 0° and 45° orientation, with little or no bioabsorbablepolymer matrix separating the layers.

FIG. 28: Scanning Electron Microscope (SEM) image using a secondaryelectron detector of Au sputtered cross section of a 6 mm pin with 85%fiber content by weight, such as those described in Example 1.Magnification 1000×. This image shows a magnification of the crosssection of reinforcing mineral fibers, with little or no bioabsorbablepolymer matrix surrounding the said fibers.

FIG. 29: Scanning Electron Microscope (SEM) image using a Back-ScatteredElectrons (BSE) detector of a cross section of a 2 mm pin with 50% fibercontent by weight, such as those described in Example 2. Magnification60×. This image shows a magnification of the edge of the pin, indicatingthat the bioabsorbable polymer is present at the outer surface of theimplant 2902.

FIG. 30 shows an example of a continuous fiber-reinforced tape of thetype that can be used to form a layer in a medical implant comprised ofcontinuous fiber-reinforced layers.

FIG. 31 shows an example of a cut-away, three-dimensional view of acontinuous fiber-reinforced tape (200).

FIG. 32a shows an example of a top-view of a reinforced bioabsorbablecomposite sheet (300) comprised of three layers of uni-directionalfibers at different angles.

FIG. 32b shows an example of a cut-away view of a reinforcedbioabsorbable composite structure (310) comprised of three layers ofuni-directional fibers at different angles.

FIG. 33 shows an example of the wall of a continuous-fiber reinforcedcomposite medical implant.

FIG. 34 shows an example of a bone filler cage that consists ofcontinuous-fiber reinforced composite medical implant walls (500) thatadditionally contains perforations (502) to allow tissue and cellularingrowth into the bone filler material (504) contained within the bonefiller cage.

FIG. 35 shows an example of a bioabsorbable cannulated screw (600) thatis a medical implant.

DETAILED DESCRIPTION

A medical implant according to at least some embodiments of the presentinvention is suitable for load-bearing orthopedic implant applicationsand comprises one or more biocomposite, optionally bioabsorbable,materials where sustained mechanical strength and stiffness are criticalfor proper implant function and wherein the implant is additionallycomprised of a moisture barrier coating that restricts or eliminatesfluid exchange into the implant.

The present invention, according to at least some embodiments, thusprovides medical implants that are useful as structural fixation forload-bearing purposes, exhibiting sustained mechanical properties as aresult of impeded degradation of the bioabsorbable materials thatcomprise the implant.

Relevant implants may include bone fixation plates, intramedullarynails, joint (hip, knee, elbow) implants, spine implants, and otherdevices for such applications such as for fracture fixation, tendonreattachment, spinal fixation, and spinal cages.

According to at least some embodiments, the herein invention relates tomedical implants comprised of a biocomposite material composition.Preferably the biocomposite material composition is comprised of (anoptionally bioabsorbable) polymer reinforced by a mineral composition.Preferably the mineral composition reinforcement is provided by areinforcing fiber made from the mineral composition.

Preferably, the medical implant or part thereof is comprised of a numberof biocomposite layers, each layer being comprised of bioabsorbablepolymer reinforced by uni-directional reinforcing fibers. The propertiesof the implant are optionally and preferably determined according to thelayer composition and structure, and the placement of the layers inregard to the device, for example with regard to layer direction. Thefibers may optionally remain discrete but optionally some melting of thepolymer may occur to bind the layers together.

A biocomposite layer can be defined as a continuous or semi-continuousstratum running through part or all of a medical implant, wherein thelayer is comprised of reinforcing fibers that aligned uni-directionally.Layers can be seen in several figures showing the internal structure ofreinforced biocomposite medical implants, including in FIGS. 7, 10, and20.

Preferably, there are between 1-100 reinforcing fibers forming thethickness of each biocomposite layer. Preferably, there are between 2-40reinforcing fibers in each layer thickness and most preferably there arebetween 4-20 reinforcing fibers.

Optionally, the directional fiber orientation between adjacent layerswithin the implant alternates between layers such that each adjacentlayer is out of phase (of a different angle) from the layer that isadjacent to it. Preferably, the average or median angle differencebetween layers is between 15 to 75 degrees, more preferably between 30to 60 degrees, and most preferably between 40 to 50 degrees. Microscopicimages of such out of phase adjacent biocomposite layers can be seen inFIGS. 26 and 27.

Preferably, the biocomposite layers within the medical implant are wellapproximated to each other. More preferably, the distance betweenlayers, as measured by the distance between the last fiber in one layersand the first fiber in the subsequent layer is between 0-200 μm, morepreferably between 0-60 μm, 1-40 μm, and most preferably between 2-30μm. Good approximation of the fibers within a layer to the fibers withinthe adjacent layer allow each layer to mechanically support the adjacentlayer. However, some distance between the layers may be desirable toallow for some polymer to remain between the fibers of adjacent layersand thus adhere the layers together, prevent layer dehiscence under highmechanical load.

The reinforcing fibers are preferably continuous fibers. Said continuousfibers are preferably longer than 4 mm, more preferably longer than 8mm, 12 mm, 16 mm, and most preferably longer than 20 mm. A microscopicimage of such continuous fibers can be seen in FIG. 22.

Alternatively, or in addition, the reinforcing fiber length can bedefined as a function of implant length wherein at least a portion ofthe reinforcing fibers, and preferably a majority of the reinforcingfibers, are of a continuous length at least 50% the longitudinal lengthof the medical implant or medical implant component that is comprised ofthese fibers. Preferably, the portion or majority of the reinforcingfibers are of continuous length at least 60% of the length of themedical implant, and more preferably at least 75% of the length of themedical implant. Such continuous reinforcing fibers can providestructural reinforcement to a large part of the implant.

The diameter of reinforcing fiber for use with herein reinforcedbiocomposite medical implant can be in the range of 0.1-100 μm.Preferably, fiber diameter is in the range of 1-20 μm. More preferably,fiber diameter is in the range of 4-16 μm.

The standard deviation of fiber diameter between fibers within themedical implant is preferably less than 5 μm, more preferably less than3 μm, and most preferably less than 1.5 μm. Uniformity of fiber diameteris beneficial for consistent properties throughout the implant.

Optionally, the distance between adjacent reinforcing fibers within abiocomposite layer is in the range of 0.5-50 μm, preferably the distancebetween adjacent fibers is in the range of 1-30 μm, more preferably inthe range of 1-20 μm, and most preferably in the range of 1-10 μm.

Preferably, the weight percentage of reinforcing fibers within thebiocomposite medical implant is in the range of 20-90%, more preferablythe weight percentage is in the range of 40%-70%

Preferably, the volume percentage of reinforcing fibers within thebiocomposite medical implant is in the range of 30-90%, more preferablythe weight percentage is in the range of 40%-70%.

While the biocomposite composition within the implant is important indetermining the mechanical and bulk properties of the implant, thespecific composition and structure that comes into contact with thesurface edge of the implant has unique significance in that thiscomposition and structure can greatly affect how surrounding cells andtissue interact with the implant following implantation into the body.For example, the absorbable polymer part of the biocomposite may behydrophobic in nature such that it will repel surrounding tissues to acertain degree while the mineral reinforcing fiber part of thebiocomposite may be hydrophilic in nature and therefore encouragesurrounding tissues to attach to the implant or create tissue ingrowth.

In an optional embodiment of the herein invention, the surface presenceof one of the compositional components by percentage of surface area isgreater than the presence of that component in the bulk composition ofthe implant by volume percentage. For example, the amount of mineral onthe surface might be greater than the amount of polymer, or vice versa.Without wishing to be limited by a single hypothesis, for greaterintegration with bone, a greater amount of mineral would optionally andpreferably be present on the surface. For reduced integration with bone,a greater amount of polymer would optionally and preferably be presenton the surface. Preferably, the percentage of surface area compositionof one component is more than 10% greater than the percentage of volumepercentage of that component in the overall biocomposite implant. Morepreferably, the percentage is more than 30% greater, and most preferablymore than 50% greater. FIG. 25 shows a microscopic image of abiocomposite medical implant with a predominance of mineral reinforcingfiber along the inner surface area edge of the implant. FIG. 29 shows amicroscopic image of a biocomposite medical implant with a predominanceof bioabsorbable polymer along the outer surface area of the implant.

Optionally, one surface of the medical implant may have a localpredominance of one of the biocomposite components while a differentsurface, or different part of the same surface, may have a localpredominance of a different biocomposite component.

Optionally, the medical implant is a threaded screw or other threadedimplant. Preferably, the outer layer of the implant will bedirectionally aligned such that the direction of the fibers approximatesthe helix angle of the threading. Preferably, the alignment angle of thefiber direction is within 45 degrees of the helix angle. Morepreferably, the alignment angle is within 30 degrees, and mostpreferably the alignment angle is within 15 degrees of the helix angle.Approximating the fiber alignment angle to the helix angle in thismanner can improve the robustness of the threading and preventdehiscence of the reinforcing fibers within the threading.

With regard to circular implants, the reinforcing fibers may optionallytake the full circular shape of the implant and curve around the circleshape of the implant without deviation from its circumference.Preferably, a portion or a majority of the reinforcing fibers deviatefrom the circle shape of the implant such that a tangential angle isformed. The tangential angle is defined as the deviation from thedirection of the curve at a fixed starting point, where the fixedstarting point is the point where the fiber touches or is closest tocoming into contact with the center of the cross-sectional circulararea. FIG. 23 depicts the tangential angle of reinforcing fibers to acannulated circular pin.

Preferably the tangential angle between reinforcing fibers within thecircular medical implant and the curvature of the implant is less than90 degrees, more preferably less than 45 degrees.

Preferably the density of the biocomposite composition for use in hereininvention is between 1 to 2 g/mL. More preferentially, density isbetween 1.2 to 1.9 g/mL. Most preferentially between 1.4 to 1.8 g/mL.

Bioabsorbable Polymers

In a preferred embodiment of the present invention, the biodegradablecomposite comprises a bioabsorbable polymer.

The medical implant described herein may be made from any biodegradablepolymer. The biodegradable polymer may be a homopolymer or a copolymer,including random copolymer, block copolymer, or graft copolymer. Thebiodegradable polymer may be a linear polymer, a branched polymer, or adendrimer. The biodegradable polymers may be of natural or syntheticorigin. Examples of suitable biodegradable polymers include, but are notlimited to polymers such as those made from lactide, glycolide,caprolactone, valerolactone, carbonates (e.g., trimethylene carbonate,tetramethylene carbonate, and the like), dioxanones (e.g.,1,4-dioxanone), δ-valerolactone, 1,dioxepanones) e.g.,1,4-dioxepan-2-one and 1,5-dioxepan-2-one), ethylene glycol, ethyleneoxide, esteramides, γ-ydroxyvalerate, β-hydroxypropionate, alpha-hydroxyacid, hydroxybuterates, poly (ortho esters), hydroxy alkanoates,tyrosine carbonates, polyimide carbonates, polyimino carbonates such aspoly (bisphenol A-iminocarbonate) and poly (hydroquinone-iminocarbonate,(polyurethanes, polyanhydrides, polymer drugs (e.g., polydiflunisol,polyaspirin, and protein therapeutics (and copolymers and combinationsthereof. Suitable natural biodegradable polymers include those made fromcollagen, chitin, chitosan, cellulose, poly (amino acids),polysaccharides, hyaluronic acid, gut, copolymers and derivatives andcombinations thereof.

According to the present invention, the biodegradable polymer may be acopolymer or terpolymer, for example: polylactides (PLA), poly-L-lactide(PLLA), poly-DL-lactide (PDLLA); polyglycolide (PGA); copolymers ofglycolide, glycolide/trimethylene carbonate copolymers (PGA/TMC); othercopolymers of PLA, such as lactide/tetramethylglycolide copolymers,lactide/trimethylene carbonate copolymers, lactide/d-valerolactonecopolymers, lactide/ε-caprolactone copolymers, L-lactide/DL-lactidecopolymers, glycolide/L-lactide copolymers (PGA/PLLA),polylactide-co-glycolide; terpolymers of PLA, such aslactide/glycolide/trimethylene carbonate terpolymers,lactide/glycolide/ε-caprolactone terpolymers, PLA/polyethylene oxidecopolymers; polydepsipeptides; unsymmetrically-3,6-substitutedpoly-1,4-dioxane-2,5-diones; polyhydroxyalkanoates; such aspolyhydroxybutyrates (PHB); PHB/b-hydroxyvalerate copolymers (PHB/PHV);poly-b-hydroxypropionate (PHPA); poly-p-dioxanone (PDS);poly-d-valerolactone-poly-ε-capralactone,poly(ε-caprolactone-DL-lactide) copolymers; methylmethacrylate-N-vinylpyrrolidone copolymers; polyesteramides; polyesters of oxalic acid;polydihydropyrans; polyalkyl-2-cyanoacrylates; polyurethanes (PU);polyvinylalcohol (PVA); polypeptides; poly-b-malic acid (PMLA):poly-b-alkanbic acids; polycarbonates; polyorthoesters; polyphosphates;poly(ester anhydrides); and mixtures thereof; and natural polymers, suchas sugars; starch, cellulose and cellulose derivatives, polysaccharides,collagen, chitosan, fibrin, hyaluronic acid, polypeptides and proteins.Mixtures of any of the above-mentioned polymers and their various formsmay also be used.

Reinforced Bioabsorbable Polymers

According to at least some embodiments of the present invention, themedical implant comprises a reinforced bioabsorbable polymer (i.e. abioabsorbable composite that includes the previously described polymerand also incorporates a reinforcing filler, generally in fiber form, toincrease the mechanical strength of the polymer).

In a more preferred embodiment of the present invention, the reinforcedbioabsorbable polymer is a reinforced polymer composition comprised ofany of the above-mentioned bioabsorbable polymers and a reinforcingfiller, preferably in fiber form. The reinforcing filler may becomprised of organic or inorganic (that is, natural or synthetic)material. Reinforcing filler may be a biodegradable glass, a cellulosicmaterial, a nano-diamond, or any other filler known in the art toincrease the mechanical properties of a bioabsorbable polymer. Thefiller is preferably made from a material or class of material otherthan the bioabsorbable polymer itself. However, it may also optionallybe a fiber of a bioabsorbable polymer itself.

Numerous examples of such reinforced polymer compositions havepreviously been documented. For example: A biocompatible and resorbablemelt derived glass composition where glass fibers can be embedded in acontinuous polymer matrix (EP 2 243 749 A1), Biodegradable compositecomprising a biodegradable polymer and 20-70 vol % glass fibers(WO2010128039 A1), Resorbable and biocompatible fiber glass that can beembedded in polymer matrix (US 2012/0040002 A1), Biocompatible compositeand its use (US 2012/0040015 A1), Absorbable polymer containingpoly[succinimide] as a filler (EP0 671 177 B1).

In a more preferred embodiment of the present invention, the reinforcingfiller is bound to the bioabsorbable polymer such that the reinforcingeffect is maintained for an extended period. Such an approach has beendescribed in US 2012/0040002 A1 and EP 2243500B1, which discusses acomposite material comprising biocompatible glass, a biocompatiblematrix polymer and a coupling agent capable of forming covalent bonds.

As noted above, the biodegradable composite and fibers are preferablyarranged in the form of biodegradable composite layers, where each layercomprises uni-directionally aligned continuous reinforcement fibersembedded in a polymer matrix comprised of one or more bioabsorbablepolymers.

The biodegradable composite layers are preferably comprised of one ormore biodegradable composite tapes, where each tape comprisesuni-directionally aligned continuous reinforcement fibers embedded in apolymer matrix comprised of one or more bioabsorbable polymers.

The biodegradable composite is preferably embodied in a polymer matrix,which may optionally comprise any of the above polymers. Optionally andpreferably, it may comprise a polymer selected from the group consistingof PLLA (poly-L-lactide), PDLLA (poly-DL-lactide), PLDLA, PGA(poly-glycolic acid), PLGA (poly-lactide-glycolic acid), PCL(Polycaprolactone), PLLA-PCL and a combination thereof. If PLLA is used,the matrix preferably comprises at least 30% PLLA, more preferably 50%,and most preferably at least 70% PLLA. If PDLA is used, the matrixpreferably comprises at least 5% PDLA, more preferably at least 10%,most preferably at least 20% PDLA.

Preferably, the inherent viscosity (IV) of the polymer matrix(independent of the reinforcement fiber) is in the range of 1.2 to 2.4dl/g, more preferably in the range of 1.5 to 2.1 dl/g, and mostpreferably in the range of 1.7 to 1.9 dl/g.

Inherent Viscosity (IV) is a viscometric method for measuring molecularsize. IV is based on the flow time of a polymer solution through anarrow capillary relative to the flow time of the pure solvent throughthe capillary.

Reinforcement Fiber

Preferably, reinforcement fiber is comprised of silica-based mineralcompound such that reinforcement fiber comprises a bioresorbable glassfiber, which can also be termed a bioglass fiber composite.

Bioresorbable glass fiber may optionally have oxide compositions in thefollowing mol. % ranges:

Na₂O: 11.0-19.0 mol. % CaO: 9.0-14.0 mol. % MgO: 1.5-8.0 mol. %

B₂O₃: 0.5-3.0 mol. %Al₂O₃: 0-0.8 mol. %P₂O₃: 0.1-0.8 mol. %

SiO₂: 67-73 mol. %

And more preferably in the following mol. % ranges:

Na₂O: 12.0-13.0 mol. % CaO: 9.0-10.0 mol. % MgO: 7.0-8.0 mol. %

B₂O₃: 1.4-2.0 mol. %P₂O₃: 0.5-0.8 mol. %

SiO₂: 68-70 mol. %

Additional optional glass fiber compositions have been describedpreviously by Lehtonen T J et al. (Acta Biomaterialia 9 (2013)4868-4877), which is included here by reference in its entirety; suchglass fiber compositions may optionally be used in place of or inaddition to the above compositions.

Additional optional bioresorbable glass compositions are described inthe following patent applications, which are hereby incorporated byreference as if fully set forth herein: Biocompatible composite and itsuse (WO2010122098); and Resorbable and blocompatible fibre glasscompositions and their uses (WO2010122019).

Optional Additional Features

The below features and embodiments may optionally be combined with anyof the above features and embodiments.Tensile strength of the reinforcement fiber is preferably in the rangeof 1200-2800 MPa, more preferably in the range of 1600-2400 MPa, andmost preferably in the range of 1800-2200 MPa.Elastic modulus of the reinforcement fiber is preferably in the range of30-100 GPa, more preferably in the range of 50-80 GPa, and mostpreferably in the range of 60-70 GPa.Fiber diameter is preferably in the range of 6-20 μm, more preferably inthe range of 10-18 μm, and most preferably in the range of 14-16 μm.Optionally, a majority of reinforcement fibers aligned to thelongitudinal axis of the medical implant are of a length of at least 50%of the total length of the implant, preferably at least 60%, morepreferably at least 75%, and most preferably at least 85%.Optionally, fibers may be aligned at an angle to the longitudinal axis(i.e. on a diagonal) such that the length of the fiber may be greaterthan 100% of the length of the implant. Optionally and preferably, amajority of reinforcement fibers are aligned at an angle that is lessthan 90, alternatively less than 60, or optionally less than 45° fromthe longitudinal axis.Preferably, the implant preferably comprises between 2-20 composite tapelayers, more preferably between 2-10 layers, and most preferably between2-6 layers; wherein each layer may be aligned in a different directionor some of the layers may be aligned in the same direction as the otherlayers.Preferably, the maximum angle between fibers in at least some of thelayers is greater than the angle between the fibers in each layer andthe longitudinal axis. For example, one layer of reinforcing fibers maybe aligned and a right diagonal to the longitudinal axis while anotherlayer may be aligned at a left diagonal to the longitudinal axis.

Compatibilizer

Optionally and preferably, the composite composition additionallyincludes a compatibilizer, which for example be such an agent asdescribed in WO2010122098, hereby incorporated by reference as if fullyset forth herein.

Biodegradable Composite Alternative Forms

Alternatively, biodegradable composite may comprise composite strandscomprising continuous reinforcement fibers or fiber bundles impregnatedwith bioabsorbable polymer. Preferably, strands are less than 1 cm indiameter. More preferably, strands are less than 8 mm, less than 5 mm,less than 3 mm, or less than 2 mm in diameter.Alternatively, biodegradable composite may comprise a woven mesh ofcontinuous reinforcement fibers wherein woven mesh is pre-impregnatedwith bioabsorbable polymer or woven mesh is comprised of reinforcementfibers and subsequently impregnated with bioabsorbable polymer.Preferably, biodegradable composite mesh layer is less than 1 cm inthickness. More preferably, impregnated mesh is less than 8 mm, lessthan 5 mm, less than 3 mm, or less than 2 mm in thickness.

Medical Implant Composite Structure

Implant may be selected from a group that includes orthopedic pins,screws, plates, intramedullary rods, hip replacement, knee replacement,meshes, etc.The average wall thickness in the implant is preferably in the range of0.2 to 10 mm, more preferably in the range of 0.4 to 5 mm, morepreferably in the range of 0.5 to 2 mm, and most preferably in the rangeof 0.5 to 1.5 mm.The implant preferably comprises between 2-20 composite tape layers,more preferably between 2-10 layers, and most preferably between 2-6layers.Optionally, implant may comprise reinforcing ribs, gussets, or struts.Rib base thickness is preferably less than 100% of the adjoining wallthickness. More preferably, thickness is less than 85%, and mostpreferably less than 75%. Rib base thickness is preferably more than 20%of adjoining wall thickness, more preferably more than 30%, and mostpreferably more than 50% of adjoining wall thickness. Preferably, ribheight is at least 2.0 times the adjoining wall thickness, morepreferably at least 3.0 times the wall thickness.Draft angle of reinforcing ribs is preferably between 0.2-0.8, morepreferably between 0.4-0.6′.Preferably, distance between ribs is at least 2 times adjoining wallthickness. More preferably, at least 3 times adjoining wall thickness.Preferably, reinforcing rib or other element increases bending stiffnessof implant by at least 20% without increasing compressive or tensilestiffness by more than 10%.Optionally, ribs along one axis, for example the longitudinal axis ofthe implant, are taller than the ribs along the perpendicular axis, forexample the latitudinal axis of the implant, in order to facilitateeasier insertion of the implant.Optionally, the implant may comprise one or more bosses to accommodatescrew insertion. Preferably, the boss is between 2-3 times the screwdiameter for self-tapping screw applications. Boss may additionallyinclude supportive gusses or ribs.Optionally, one or more sides of implant may be textured.Optionally, implant may contain continuous fibers aligned in a circulararrangement around holes, such as screw or pin holes, within theimplant.

Perforated Implant Part Walls

In some medical implants, it is desirable for there to be cellular ortissue ingrowth through the implant so as to strengthen theincorporation of the implant into the tissue and to increase complianceof the implant in physiological function. In order to further promotesuch ingrowth, it is beneficial to have gaps or holes in the walls ofthe herein described medical implant.Preferably, if present, such perforations in implant walls comprise atleast 10% of the surface area of the implant, more preferably at least20%, at least 30%, at least 40%, or at least 50% of the surface area ofthe implant.In one optional embodiment of the present invention, the implant is ascrew and the fenestrations of the threading contain perforation.In one embodiment of the present invention, the implant containsperforations between composite tapes or between the reinforcement fiberswithin composite tapes making up the implant.In a preferred embodiment, a majority of perforations are betweenreinforcement fibers and do not penetrate reinforcement fibers.

Cages Full of Bone Filler

In another embodiment of herein invention, the implant comprises anorthopedic implant and the implant forms a partial or full container andan osteoconductive or osteoinductive material is contained within theimplant container.In a preferred embodiment, the implant container is additionallyperforated so as to allow improved bone ingrowth into theosteoconductive or osteoinductive material contained within the implantcage.In an optional embodiment, the implant comprises an opening or doorthrough which bone filler can be introduced and/or bone ingrowth cantake place.In an optional embodiment, the implant comprises two or more discreteparts or separate parts joined by a joint such that implant cage may befilled with bone filler material and subsequently assembled or closed totrap bone filler inside.Framework of Continuous Fiber Reinforced Structure with Non-ReinforcedSurrounding MaterialWhereas continuous fiber reinforced bioabsorbable composite structuresprovide the optimal mechanical strength and stiffness to a medicalimplant, it may also be beneficial in certain cases to have additionalfeatures or layers in the medical implant that cannot be made fromcontinuous fiber reinforced composite tapes. In such cases, themechanical strength of the continuous fiber reinforced bioabsorbablecomposite structures can be incorporated into the implant but additionalsections or layers of non-reinforced polymer may be added to improve orcustomize the implant. These sections or layers are preferably added tothe implant either by overmolding onto the structure or by 3-D printingonto the structure.In one embodiment of the present invention, medical implant comprises astructural support comprised of a continuous fiber-reinforcedbioabsorbable composite material and additionally comprises a section orlayer comprised of non-reinforced polymer material.Optionally the second layer functions as a bone interface layercomprised of a non-reinforced absorbable polymer material. Alsooptionally the structural support and non-reinforced polymer section areeach fabricated using a different production technique. Also optionallythe structural support is fabricated by machining, compression molding,or composite flow molding and the interface layer is fabricated byinjection molding or 3D printing; optionally the interface layer isfabricated on top of the prefabricated structural support.Optionally the non-reinforced polymer section is a bone interface layerand dimensions of the interface layer are partially or entirelydetermined by the bone geometry of a specific patient or patientpopulation.Optionally the bone geometry of patient or patient population isdetermined by measuring through imaging technique such as X-Ray, CT,MRI.Optionally the elastic modulus and/or flexural strength of structuralsupport is at least 20% greater than that of the non-reinforced polymersection.Optionally, continuous-fiber reinforced composite material in implant iscoated with a polymer resin wherein the polymer resin on fiber in thecomposite material has a higher or lower melting temp than the flowablematrix resin; or polymer resin on fiber has slower or faster degradationrate than flowable matrix resin; or polymer resin on fiber is morehydrophobic or more hydrophilic than flowable matrix resinIn an optional embodiment, an additional section or layer is comprisedof a reinforced polymer but where polymer is reinforced bynon-continuous fibers, preferably fibers less than 10 mm in length, andmore preferably less than 5 mm in length.In an optional embodiment, an additional section or layer ofnon-reinforced or non-continuous fiber reinforced polymer additionalcomprises an additive.Optionally, additive comprises an osteoconductive material orcombination of osteoconductive materials such as beta tricalciumphosphate, calcium phosphate, hydroxyapatite, decellularized bone.Optionally, the additive comprises an anti-microbial agent or boneinducing agent.

Production Method

Continuous-fiber reinforced bioabsorbable implants may optionally beproduced using any method known in the art. Preferably, implant isprimarily produced by method other than injection molding. Morepreferably, implant is primarily produced using manufacturing methodthat subjects implant to compressive pressure, such as compressionmolding. Preferably, prior to compressive molding, a multi-layerstructure is constructed from such composite material by wrapping orother method of adding layers, such that the reinforcement fibers are intension following such layering.Preferably, moisture content of implant following compression molding isless than 30%, more preferably less than 20%, even more preferably lessthan 10%, 8%, 6%, 5%.Implant Contact with Surrounding TissueIn an optional embodiment of the present invention, less than 100% ofimplant surface area is in contact with surrounding tissue. This may beclinically desirable for several reasons:1. Reduced friction with surrounding tissue upon insertion, easinginsertion2. Reduced bone contact can reduce interference to bone surface bloodflowIn a preferred embodiment, implant contains surface protrusion elementsof at least 0.1 mm in height and less than 2 mm in height that come intocontact with tissue surrounding implant.Preferably, total percentage of surface area of implant that comes intocontact with surrounding tissue is less than 80%, more preferably lessthan 60%, 50%, 40%, 30%.

Balloons

In an optional embodiment of herein invention, implant additionallycomprises a balloon. Balloon walls are preferably comprised of between1-3 layers of reinforced composite.

Fabrication of the Implant

Any of the above-described bioabsorbable polymers or reinforcedbioabsorbable polymers may be fabricated into any desired physical formfor use with the present invention. The polymeric substrate may befabricated for example, by compression molding, casting, injectionmolding, pultrusion, extrusion, filament winding, composite flow molding(CFM), machining, or any other fabrication technique known to thoseskilled in the art. The polymer may be made into any shape, such as, forexample, a plate, screw, nail, fiber, sheet, rod, staple, clip, needle,tube, foam, or any other configuration suitable for a medical device.

Load-Bearing Mechanical Strength

The herein invention particularly relates to bioabsorbable compositematerials that can be used in medical applications that require highstrength and a stiffness compared to the stiffness of bone. Thesemedical applications require the medical implant to bear all or part ofthe load applied by or to the body and can therefore be referred togenerally as “load-bearing” applications. These include fracturefixation, tendon reattachment, joint replacement, spinal fixation, andspinal cages.

The flexural strength preferred from the herein described load-bearingmedical implant is at least 200 MPa, preferably above 400 MPa, morepreferably above 600 MPa, and even more preferably above 800 MPa. TheElastic Modulus (or Young's Modulus) of the bioabsorbable composite foruse with herein invention is preferably at least 10 GPa, more preferablyabove 15 GPa, and even more preferably above 20 GPa but not exceeding100 GPa and preferably not exceeding 60 GPa.

Sustained Mechanical Strength

There is a need for the bioabsorbable load-bearing medical implants ofthe herein invention to maintain their mechanical properties (highstrength and stiffness) for an extended period to allow for sufficientbone healing. The strength and stiffness preferably remains above thestrength and stiffness of cortical bone, approximately 150-250 MPa and15-25 GPa respectively, for a period of at least 3 months, preferably atleast 6 months, and even more preferably for at least 9 months in vivo(i.e. in a physiological environment).

More preferably, the flexural strength remains above 400 MPa and evenmore preferably remains above 600 MPa.

In another embodiment of the present invention, the mechanical strengthdegradation rate of the coated medical implant approximates the materialdegradation rate of the implant, as measured by weight loss of thebiodegradable composite.

In a preferred embodiment, the implant retains greater than 50% of itsmechanical strength after 3 months of implantation while greater than50% of material degradation and hence weight loss occurs within 12months of implantation.

In a preferred embodiment, the implant retains greater than 70% of itsmechanical strength after 3 months of implantation while greater than70% of material degradation and hence weight loss occurs within 12months of implantation.

In a preferred embodiment, the implant retains greater than 50% of itsmechanical strength after 6 months of implantation while greater than50% of material degradation and hence weight loss occurs within 9 monthsof implantation.

In a preferred embodiment, the implant retains greater than 70% of itsmechanical strength after 6 months of implantation while greater than70% of material degradation and hence weight loss occurs within 9 monthsof implantation.

The mechanical strength degradation and material degradation (weightloss) rates of the medical implant can be measured after in vivoimplantation or after in vitro simulated implantation. In the case of invitro simulated implantation, the simulation may be performed in realtime or according to accelerated degradation standards.

“Biodegradable” as used herein is a generalized term that includesmaterials, for example polymers, which break down due to degradationwith dispersion in vivo.

The decrease in mass of the biodegradable material within the body maybe the result of a passive process, which is catalyzed by thephysicochemical conditions (e.g. humidity, pH value) within the hosttissue. In a preferred embodiment of biodegradable, the decrease in massof the biodegradable material within the body may also be eliminatedthrough natural pathways either because of simple filtration ofdegradation by-products or after the material's metabolism(“Bioresorption” or “Bioabsorption”). In either case, the decrease inmass may result in a partial or total elimination of the initial foreignmaterial. In a preferred embodiment, said biodegradable compositecomprises a biodegradable polymer that undergoes a chain cleavage due tomacromolecular degradation in an aqueous environment.

A polymer is “absorbable” within the meaning of this invention if it iscapable of breaking down into small, non-toxic segments which can bemetabolized or eliminated from the body without harm. Generally,absorbable polymers swell, hydrolyze, and degrade upon exposure tobodily tissue, resulting in a significant weight loss. The hydrolysisreaction may be enzymatically catalyzed in some cases. Completebioabsorption, i.e. complete weight loss, may take some time, althoughpreferably complete bioabsorption occurs within 24 months, mostpreferably within 12 months.

The term “polymer degradation” means a decrease in the molecular weightof the respective polymer. With respect to the polymers, which arepreferably used within the scope of the present invention saiddegradation is induced by free water due to the cleavage of ester bonds.The degradation of the polymers as for example used in the biomaterialas described in the examples follows the principle of bulk erosion.Thereby a continuous decrease in molecular weight precedes a highlypronounced mass loss. Said mass loss is attributed to the solubility ofthe degradation products. Methods for determination of water inducedpolymer degradation are well known in the art such as titration of thedegradation products, viscometry, differential scanning calorimetry(DSC).

The term “Biocomposite” as used herein is a composite material formed bya matrix and a reinforcement of fibers wherein both the matrix andfibers are biocompatible and optionally bioabsorbable. In most cases,the matrix is a polymer resin, and more specifically a syntheticbioabsorbable polymer. The fibers are optionally and preferably of adifferent class of material (i.e. not a synthetic bioabsorbablepolymer), and may optionally comprise mineral, ceramic, cellulosic, orother type of material.

Clinical Applications

The medical implants discussed herein are generally used for bonefracture reduction and fixation to restore anatomical relationships.Such fixation optionally and preferably includes one or more, and morepreferably all, of stable fixation, preservation of blood supply to thebone and surrounding soft tissue, and early, active mobilization of thepart and patient.

There are several exemplary, illustrative, non-limiting types of bonefixation implants for which the materials and concepts describedaccording to at least some embodiments of the present invention may berelevant, as follows:

Bone Plate

A bone plate is typically used to maintain different parts of afractured or otherwise severed bone substantially stationary relative toeach other during and/or after the healing process in which the bonemends together. Bones of the limbs include a shaft with a head at eitherend thereof. The shaft of the bone is generally elongated and ofrelatively cylindrical shape.

It is known to provide a bone plate which attaches to the shaft or headand shaft of a fractured bone to maintain two or more pieces of the bonein a substantially stationary position relative to the one another. Sucha bone plate generally comprises a shape having opposing substantiallyparallel sides and a plurality of bores extending between the opposingsides, wherein the bores are suitable for the receipt of pins or screwsto attach the plate to the bone fragments.

For proper function of the bone plate in maintaining different parts ofa fractured bone stationary relative to each other, the plate must be ofsufficient mechanical strength and stiffness to maintain the position ofthe bone fragments or pieces. However, it must achieve these mechanicalproperties within a low profile thickness profile to ensure that therewill be sufficient space for the bone plate to fit between bone and thesurrounding soft tissue. The thickness of the bone plate is generally inthe range of 2.0 mm to 8.0 mm and more commonly in the range of 2.0 mmto 4.0 mm. The widths of the plates are variable but

Screws

Screws are used for internal bone fixation and there are differentdesigns based on the type of fracture and how the screw will be used.Screws come in different sizes for use with bones of different sizes.Screws can be used alone to hold a fracture, as well as with plates,rods, or nails. After the bone heals, screws may be either left in placeor removed.

Screws are threaded, though threading can be either complete or partial.Screws can include compression screws, locking screws, and/or cannulatedscrews. External screw diameter can be as small as 0.5 or 1.0 mm but isgenerally less than 3.0 mm for smaller bone fixation. Larger bonecortical screws can be up to 5.0 mm and cancellous screws can even reach7-8 mm. Some screws are self-tapping and others require drilling priorto insertion of the screw. For cannulated screws, a hollow section inthe middle is generally larger than 1 mm diameter in order toaccommodate guide wires.

Wires/Pins

Wires are often used to pin bones back together. They are often used tohold together pieces of bone that are too small to be fixed with screws.They can be used in conjunction with other forms of internal fixation,but they can be used alone to treat fractures of small bones, such asthose found in the hand or foot. Wires or pins may have sharp points oneither one side or both sides for insertion or drilling into the bone.

“K-wire” is a particular type of wire generally made from stainlesssteel, titanium, or nitinol and of dimensions in the range of 0.5-2.0 mmdiameter and 2-25 cm length. “Steinman pins” are general in the range of2.0-5.0 mm diameter and 2-25 cm length. Nonetheless, the terms pin andwire for bone fixation are used herein interchangeably.

Anchors

Anchors and particularly suture anchors are fixation devices for fixingtendons and ligaments to bone. They are comprised of an anchormechanism, which is inserted into the bone, and one or more eyelets,holes or loops in the anchor through which the suture passes. This linksthe anchor to the suture. The anchor which is inserted into the bone maybe a screw mechanism or an interference mechanism. Anchors are generallyin the range of 1.0-6.5 mm diameter

Cable, Ties, Wire Ties

Cables, ties, or wire ties can be used to perform fixation by cerclage,or binding, bones together. Such implants may optionally hold togetherbone that cannot be fixated using penetration screws or wires/pin,either due to bone damage or presence of implant shaft within bone.Generally, diameter of such cable or tie implants is optionally in therange of 1.0 mm-2.0 mm and preferably in the range of 1.25-1.75 mm. Wiretie width may optionally be in the range of 1-10 mm.

Nails or Rods

In some fractures of the long bones, medical best practice to hold thebone pieces together is through insertion of a rod or nail through thehollow center of the bone that normally contains some marrow. Screws ateach end of the rod are used to keep the fracture from shortening orrotating, and also hold the rod in place until the fracture has healed.Rods and screws may be left in the bone after healing is complete. Nailsor rods for bone fixation are generally 20-50 cm in length and 5-20 mmin diameter (preferably 9-16 mm). A hollow section in the middle of nailor rod is generally larger than 1 mm diameter in order to accommodateguide wires.

Any of the above-described bone fixation implants may optionally be usedto fixate various fracture types including but not limited to comminutedfractures, segmental fractures, non-union fractures, fractures with boneloss, proximal and distal fractures, diaphyseal fractures, osteotomysites, etc.

Example #1—Large Diameter Pins

Below example describes production of large diameter orthopedic pinswith reinforced biocomposite materials. This example demonstrates howdifferent medical implant pins comprised of reinforced biocompositematerials can have different performance properties with regard toflexural modulus and strength, both at time zero (following production)and following simulated degradation, relating to the compositionalstructure, geometry, and composition of each type of pin.

Materials & Methods

Three types of pin implants, each of outer diameter 6 mm and 5 cm lengthwere produced using reinforced composite material. Material compositewas comprised of PLDLA 70/30 polymer reinforced with 50% w/w, 70%, or85% w/w continuous mineral fibers. Mineral fibers composition wasapproximately Na₂O 14%, MgO 5.4%, CaO 9%, B₂O₃ 2.3%, P₂O₅ 1.5%, and SiO₂67.8% w/w. Testing samples were manufactured by compression molding ofmultiple layers of composite material into a tubular mold, either withor without a 3 mm pin insert in the center. Each layer was comprised ofthe PLDLA polymer with embedded uni-directionally aligned continuousfibers. Orientation of layers relative to longitudinal axis of implantwere 0° (parallel to implant longitudinal axis), 45°, 0°, −45° 0°, in arepetitive manner according to number of layers in the implant. Eachlayer was approximately 0.18 mm thick. Three (3) pin samples wereproduced for each pin group.

Implant samples were tested in a tensile testing system (220Q1125-95,TestResources, MN, USA) for flexural strength, flexural modulus andmaximum flexural load according to modified standard test method, ASTMD790 (Standard Test Methods for Flexural Properties of Unreinforced andReinforced Plastics and Electrical Insulating Materials,http://www.astm.org/Standards/D790.htm, ASTM International, PA, USA).Testing was conducted initially and following simulated in vitrodegradation according to modified ASTM F1635 (Standard Test Method forin vitro Degradation Testing of Hydrolytically Degradable Polymer Resinsand Fabricated Forms for Surgical Implants,http://www.astm.org/Standards/F1635.htm ASTM International, PA, USA),wherein samples were incubated in simulated body fluid (SBF), 142 Na⁺, 5K⁺, 1.5 Mg^(2+,) 2.5 Ca²⁺, 147.8 Cl⁻, 4.2 HCO₃ ⁻, 1 HPO₄ ³⁻, 0.5 SO₄ ²⁻mol/m³, for 5 days at a temperature of 50° C., while shaking at 30 rpm.Mechanical testing was performed using a 5KN load cell and anappropriate fixture for three point bending testing. Sample span was 40mm at the beginning of the test and cross head speed was set at 2mm/min. Dimensions, weight and density of samples were recorded.

Scanning electron microscope (SEM) (FEI Quanta FEG 250, Holland) imageswere captured for cross-sections of implant samples at severalmagnifications, with and without Au sputtering, and using either SE orBSE detectors. ImageJ™ (NIH Image Processing Software,http://www.imagej.nih.gov/ij/, National Institute of Health, Maryland,USA) was used to count or measure the following parameters:

-   -   1. Distance between fibers    -   2. Distance between layers    -   3. Number of fibers per layer    -   4. Fiber diameter    -   5. Tangential angle to curvature        MATLAB (http://www.mathworks.com/products/matlab/, Mathworks,        MA, USA) was used to count or measure the following parameters:    -   1. Volume Distribution of Fibers within Cross Section of Implant

Results

Table 1a shows the mechanical performance results of implant pins madefrom three different types of reinforced composites as described above.The structural properties of these implants are described by theproduction methods discussed above and their internal compositions areseen in the associated images. Quantification of several parametersrelated to the internal composition structure of the implants can beseen in table 1b.

TABLE 1a Mean values and standard deviations of the mechanicalproperties and bulk properties of the implants (n = 3). Flexural MaxStrength Load Density Volume Pin Type E [MPa] [MPa] [N] [gr/ml] [mm³]Full pin. OD  8697.0 ± 243.7 ± 14.5 549.6 ± 1.60 1472.7 6 mm. 50% w/w237.8 57.3 fiber. T = 0 Full pin. OD  6423.5 ± 118.6 ± 16.6 267.9 ± 1.641480.5 6 mm. 50% w/w 243.6 41.3 fiber. T = 5 d Full pin. OD 14207.5 ±224.6 ± 51.6 455.1 ± 1.83 1365.9 6 mm. 70% w/w 811.7 130.5 fiber. T = 0Full pin. OD  6745.0 ±  85.1 ± 15.2 209.7 ± 1.78 1567.7 6 mm. 70% w/w677.6 48.6 fiber. T = 5 d Hollow pin. OD  7244.6 ± 148.5 ± 5.4  294.0 ±1.58 1067.4 6 mm. ID 1736.9 5.1 3 mm. 50% w/w fiber. T = 0 Hollow pin.OD  4281.6 ±  81.2 ± 12.5 169.6 ± 1.63 1113.1 6 mm. ID 1608.2 27.4 3 mm.50% w/w fiber. T = 5 dFull pin samples produced with OD 6 mm, 85% w/w fiber severely lacked incohesive strength, likely due to insufficient amount of polymer bindingbetween fiber layers. These samples failed during loading onto thetensile testing system and therefore mechanical property results werenot recorded. Images of these pins can be seen in FIGS. 27 and 28, whichshow high amount of fibers and absence of polymer.As can be seen in Table IA, incubation for 5 days in SBF at 50° C.,which accelerates degradation rate, resulted in a decrease in modulus of26%, 53% and 41% in the full 0.50% w/w, full 70% w/w and hollow 6 mmpins respectively. Incubation for 5 days in SBF at 50° C. whichaccelerates degradation rate, resulted in a decrease in flexuralstrength of 51%, 62% and 45% in the full 50% w/w, full 70% w/w andhollow 6 mm pins respectively. Incubation for 5 days in SBF at 50° C.,which accelerates degradation rate, resulted in a decrease in maximumflexural load of 51%, 53% and 42% in the full 50% w/w, full 70% w/w andhollow 6 mm pins respectively.

TABLE 1b Measured structural parameters relating the reinforcing fibersand biocomposite layers within two types of biocomposite pins. FiberDistance Distance diameter between Fibers in Layer between range fiberslayer thickness layers (μm) (μm) thickness (μm) (μm) Full 9.38- 1.39-8.77-9 92.6-185.0 28.77- pin. OD 12.83 (FIG. 2) (FIG. 3) (FIG. 3, 4) 50.056 mm. 50% (FIG. 1) (FIG. 5) w/w fiber Full 4.63- 9- 161.52 (FIG. pin. OD31.45 (FIG. 13 (FIG. 7) 6 mm. 70% 6) 7) w/w fiberWithout wishing to be limited by a single hypothesis, it is believedthat reinforcing fiber content, diameter, distribution, and arrangementinto layers seen in this example (Example 1) were the cause or at leasta significantly contributing factor.Specifically with regard to reinforcing fiber, increasing reinforcingfiber content may contribute positively to mechanical properties of amedical implant, as seen by the stronger and stiffer samples producedwith 70% fiber as compared with those produced with 50% fiber. However,the 70% fiber implants seemed to lose mechanical properties at a fasterrate. Thus, there are potential benefits to each of these amount offibers. Above a certain point, overly high fiber content can result infailure of the implant, as observed with the 85% fiber pins.

Example #2—Small Diameter Pins

Below example describes production of small diameter orthopedic pinswith reinforced biocomposite materials. This example demonstrates howdifferent medical implant pins comprised of reinforced biocompositematerials can have different performance properties with regard toflexural modulus and strength, both at time zero (following production)and following simulated degradation (for example upon insertion to thebody), relating to the compositional structure, geometry, andcomposition of each type of pin.

Materials & Methods

Three types of pin implants, each of outer diameter 2 mm and 5 cm lengthwere produced using reinforced composite material. Material compositewas comprised of PLDLA 70/30 polymer reinforced with 50% w/w or 70% w/wcontinuous mineral fibers. Mineral fiber composition was approximatelyNa₂O 14%, MgO 5.4%, CaO 9%, B₂O₃ 2.3%, P₂O₅ 1.5%, and SiO₂ 67.8% w/w.Testing samples were manufactured by compression molding of multiplelayers of composite material into a tubular mold, either with or withouta 1 mm pin insert in the center. Each layer was comprised of the PLDLApolymer with embedded uni-directionally aligned continuous fibers.Orientation of layers relative to longitudinal axis of implant were 0°(parallel to implant longitudinal axis), 45°, 0°, −45°, 0°, in arepetitive manner according to number of layers in the implant. Eachlayer was approximately 0.18 mm thick. Three (3) pin samples wereproduced for each pin group.

Implant samples were tested in a tensile testing system (220Q1125-95,TestResources, MN, USA) for flexural strength, flexural modulus andmaximum flexural load according to modified standard test method, ASTMD790 (Standard Test Methods for Flexural Properties of Unreinforced andReinforced Plastics and Electrical Insulating Materials,http://www.astm.org/Standards/D790.htm. ASTM International, PA, USA).Testing was conducted initially and following simulated in vitrodegradation according to modified ASTM F1635, (Standard Test Method forin vitro Degradation Testing of Hydrolytically Degradable Polymer Resinsand Fabricated Forms for Surgical Implants,http://www.astm.org/Standards/F1635.htm ASTM International, PA, USA)wherein samples were incubated in simulated body fluid (SBF), 142 Na⁺, 5K⁺, 1.5 Mg²⁺, 2.5 Ca²⁺, 147.8 Cl⁻, 4.2 HCO₃ ⁻, 1 HPO₄ ³⁻, 0.5 SO₄ ²⁻mol/m³, for 5 days at a temperature of 50° C., while shaking at 30 rpm.Mechanical testing was performed using a 500 N load cell and anappropriate fixture for three point bending testing. Sample span was 40mm at the beginning of the test and cross head speed was set at 2mm/min. Dimensions, weight and density of samples were recorded.

Scanning electron microscope (SEM) (FEI Quanta FEG 250, Holland) imageswere captured for cross-sections of implant samples at severalmagnifications, with and without Au sputtering, and using either SE orBSE detectors. ImageJ™ (NIH Image Processing Software,http://www.imagej.nih.gov/ij/, National Institute of Health, Maryland,USA) was used to count or measure the following parameters:

-   -   1. Distance between fibers    -   2. Distance between layers    -   3. Number of fibers per layer    -   4. Fiber diameter    -   5. Tangential angle to curvature        MATLAB (http://www.mathworks.com/products/matlab/, Mathworks,        MA, USA) was used to count or measure the following parameters:    -   1. Volume distribution of fibers within cross section of        implant: The percentage of fiber to polymer was calculated by        summing the entire fiber area in the image divided by the area        of the entire implant cross section in the image.

Percentage of Fiber to Polymer=Sum of Fiber AreaArea of Entire CrossSection*100 Results

Table 2a shows the mechanical performance results of three differenttypes of reinforced composites implant pins produced as described above.The structural properties of these implants are described by theproduction methods discussed above and their internal compositions areseen in the associated images. Quantification of several parametersrelated to the internal composition structure of the implants can beseen in tables 2b, c and d.

TABLE 2a Mean values and standard deviations of the mechanicalproperties and bulk properties of the implants (n = 3). Flexural EStrength Max Load Density Volume Pin Type [MPa] [MPa] [N] [gr/ml] [mm³]Full pin. OD 273.6 ± 11761.0 ±  25.7 ± 3.79 1.43 180.7 2 mm. 50% w/w48.3 1028.8 fiber. T = 0 Full pin. OD 127.2 ± 11954.9 ± 12.45 ± 2.4 1.37 185.88 2 mm. 50% w/w 23.4 2885.5 fiber. T = 5 d Full pin. OD 290.6± 14062.2 ± 30.16 ± 1.55 192.43 2 mm. 70% w/w 2.7 2158.3 1.6 fiber. T =0 Full pin. OD  78.9 ±  9931.5 ± 8.65 ± 1.2 1.57 201.7 2 mm. 70% w/w14.4 358.8 fiber. T = 5 d Hollow pin. OD 136.6 ± 10231.3 ± 14.1 ± 1.11.37 157.6 2 mm. ID 11.7 1609.2 1 mm. 50% w/w fiber. T = 0 Hollow pin.OD 100.1 ±  6913.7 ± 10.35 ± 1.56 158.1 2 mm. ID 16.5 2420.1 2.11 1 mm.50% w/w fiber. T = 5 dIncubation for 5 days in SBF at 50° C., which accelerates degradationrate, resulted in a decrease in flexural strength of 54%, 27% and 73% inthe full 50% w/w, full 70% w/w and hollow 2 mm pins respectively.Incubation for 5 days in SBF at 50° C., which accelerates degradationrate, resulted in a decrease in maximum flexural load of 52% 27% and 71%in the full 50% w/w, full 70% w/w and hollow 2 mm pins respectively.Incubation for 5 days in SBF at 50° C., which accelerates degradationrate, resulted in a decrease in flexural modulus of 32% and 29% in thefull 70% w/w and hollow 2 mm 50% w/w pins respectively.

TABLE 2b Measured structural parameters relating the reinforcing fibersand biocomposite layers within a biocomposite pin Fiber DistanceDistance diameter between Fibers in Layer between range fibers layerthickness layers (μm) (μm) thickness (μm) (μm) Full 10.18- 2.80-16.024-6 91.09 (FIG. 14.35- pin. OD 13.5 (FIG. 9)  (FIG. 10) 10) 41.59 2 mm.50% (FIG. 8)  (FIG. 12) w/w fiber Hollow 11-15 2.04- 11.96- pin. OD(FIG. 13) 10.11 33.6 2 mm, ID (FIG. 14) (FIG. 16) 1 mm. 50% w/w fiber

TABLE 2c Measured volume percentage of fiber as measured fromcross-section of biocomposite full pin implant of OD 2 mm, 50% w/w fiber(see FIG. 11) Area of Entire Percentage of Cross Section Sum of FiberArea Remaining Area Fiber to Polymer 22579 μm 11043 μm 1.1536e+04 μm48.90%

TABLE 2d Measured volume percentage of fiber as measured fromcross-section of biocomposite full plate implant of OD 2 mm, ID 1 mm,50% w/w fiber (see FIG. 15) Area of Entire Percentage of Cross SectionSum of Fiber Area Remaining Area Fiber to Polymer 14094 μm 9645.14 μm4448.86 μm 68.43%Without wishing to be limited by a single hypothesis, it is believedthat reinforcing fiber content, diameter, distribution, and arrangementinto layers seen in this example (Example 2) were the cause or at leasta significantly contributing factor.This example also suggests a potential structural difference betweendifferent implant part geometries (between a full pin and cannulatedpin), where it is optionally possible for reinforcing fiber layers inthe biocomposite implant to arrange and align themselves in differentialmanners depending on the shape of the implant and the forces that theimplant is exposed to during its production.

Example #3—Plates

Below example describes production of thin orthopedic plates withreinforced biocomposite materials. This example demonstrates howdifferent medical implant plates comprised of reinforced biocompositematerials can have different performance properties with regard toflexural modulus and strength, both at time zero (following production)and following simulated degradation, relating to the compositionalstructure, geometry, and composition of each type of plate.

Materials & Methods

Four types of plate implants, each with a thickness of 2 mm, width of12.8 mm and 6 cm length were produced using reinforced compositematerial. Material composite was comprised of PLDLA 70/30 polymerreinforced with 50% w/w or 70% w/w continuous mineral fibers. Mineralfibers composition was approximately Na₂O 14%, MgO 5.4%, CaO 9%, B₂O₃2.3%, P₂O₅ 1.5%, and SiO₂ 67.8% w/w. Testing samples were manufacturedby compression molding of multiple layers of composite material into arectangle mold. Each layer was comprised of the PLDLA polymer withembedded uni-directionally aligned continuous fibers. Orientation oflayers relative to longitudinal axis of implant were 0° (parallel toimplant longitudinal axis), 45°, 0°, −45°, 0°, in a repetitive manneraccording to number of layers in the implant. Each layer wasapproximately 0.18 mm thick. For the amorphous plates, continuous fiberswere cut to small pieces, mixed and molded. Three (3) plate samples wereproduced for each plate group.

Implant samples were tested in a tensile testing system (220Q1125-95,TestResources, MN, USA) for flexural strength, flexural modulus andmaximum flexural load according to modified standard test method, ASTMD790 (Standard Test Methods for Flexural Properties of Unreinforced andReinforced Plastics and Electrical Insulating Materials,http://www.astm.org/Standards/D790.htm, ASTM International, PA, USA).Testing was conducted initially and following simulated in vitrodegradation according to modified ASTM F1635, (Standard Test Method forin vitro Degradation Testing of Hydrolytically Degradable Polymer Resinsand Fabricated Forms for Surgical Implants,http://www.astm.org/Standards/F1635.htm ASTM International, PA, USA)wherein samples were incubated in simulated body fluid (SBF), 142 Na⁺, 5K⁺, 1.5 Mg²⁺, 2.5 Ca²⁺, 147.8 Cl⁻, 4.2 HCO₃ ⁻, 1 HPO₄ ³⁻, 0.5 SO₄ ²⁻mol/m³, for 5 days at a temperature of 50° C., while shaking at 30 rpm.Mechanical testing was performed using a 5 KN load cell and anappropriate fixture for three point bending testing. Sample span was 40mm at the beginning of the test and cross head speed was set at 2mm/min. Dimensions, weight and density of samples were recorded.

Scanning electron microscope (SEM) (FEI Quanta FEG 250, Holland) imageswere captured for cross-sections of implant samples at severalmagnifications, with and without Au sputtering, and using either SE orBSE detectors. ImageJ™ (NIH Image Processing Software,http://www.imagej.nih.gov/ij/, National Institute of Health, Maryland,USA) was used to count or measure the following parameters:

-   -   1. Distance between fibers    -   2. Distance between layers    -   3. Number of fibers per layer    -   4. Fiber diameter    -   5. Tangential angle to curvature        MATLAB (http://www.mathtworks.com/products/matlab/, Mathworks,        MA, USA) was used to count or measure the following parameters:    -   1. Volume distribution of fibers within cross section of implant

Results

Table 3a shows the mechanical performance results of three differenttypes of reinforced composites implant pins produced as described above.The structural properties of these implants are described by theproduction methods discussed above and their internal compositions areseen in the associated images. Quantification of several parametersrelated to the internal composition structure of the implants can beseen in table 3b.

TABLE 3a Mean values and standard deviations of the mechanicalproperties and bulk properties of the implants (n = 3). Flexural Max EStrength Load Density Volume Plate Type [MPa] [MPa] [N] [gr/ml] [mm³]Plate. 50% w/w 306.9 ± 15362.1 ± 285.27 ± 1.65 1624.8 fiber. T = 0 13.9502.4 7.7 Plate. 50% w/w 127.0 ± 11063.3 ±  143.5 ± 1.6 1786 fiber. T =5 d 39.1 688.8 41.7 Plate. 70% w/w 358.5 ± 23088.4 ± 307.56 ± 1.891552.0 fiber. T = 0 142.9 2012.5 121 Plate. 70% w/w  83.2 ± 10806.9 ±115.76 ± 1.7 1947.7 fiber. T = 5 d 34.3 1463.3 115.8 Plate. Amorphous108.1 ± 8299.7 ±  97.4 ± 1.66 1595.1 50% w/w fiber. 16.5 1276.9 17.0 T =0Incubation for 5 days in SBF at 50° C., which accelerates degradationrate, resulted in a decrease in flexural modulus of 27% and 53% in thefull 50% w/w and full 70% w/w plates respectively. Incubation for 5 daysin SBF at 50° C., which accelerates degradation rate, resulted in adecrease in flexural strength of 58% and 76% in the full 50% w/wand full70% w/w plates respectively.Incubation for 5 days in SBF at 50° C., which accelerates degradationrate, resulted in a decrease in maximum flexural load of 50% and 62% inthe full 50% w/w and full 70% w/w plates respectively.For this geometry and production method it seems that the increase infiber content from 50% to 70 w/w, increases the initial mechanicalstrength but accelerates the degradation process.Having short non oriented fibers as exist in the amorphous plate versuscontinuously oriented fibers resulted in a decrease of 46%, 65% and 66%in the modulus, flexural strength and maximum load for a similar densityand production conditions.

TABLE 3b Measured structural parameters relating the reinforcing fibersand biocomposite layers within a biocomposite plate Fiber Distancediameter Distance Fibers in Layer between range between layer thicknesslayers (μm) fibers (μm) thickness (μm) (μm) Plate. 50% 11.48- 2.32 - w/wfiber 13.98 (FIG. 9.88 (FIG. 17) 18) Plate. 70% 3.04- 6- 70.03- 3.77-w/w fiber 20 (FIG. 10 (FIG. 110.86 15.99 (FIG. 19) 20) (FIG. 20) 21)

Example #4—Degradation Differences

Below example describes the degradation of orthopedic implants producedwith reinforced biocomposite materials. This example demonstrates howdifferent medical implants comprised of reinforced biocompositematerials can differ in performance properties with regards to materialloss and swelling ratio following simulated degradation. An absorbableorthopedic implant, used for bone fixation, as intended for thefollowing, ideally needs to retain its strength for the period neededfor the bone to heal, and then gradually degrade and lose its strengthas it is replaced by bone. Material weight loss is an indication for therate of degradation. Swelling ratio is an indication for conformationalchanges, hydrophilicity as well as an indication for porosity. Controlof both parameters are important for implant design.

Materials & Methods

Pin and plate implants were produced using reinforced composite materialas described in example 1-3. Material composite was comprised of PLDLA70/30 polymer reinforced with 50% w/w or 70% w/w continuous mineralfibers. Mineral fibers composition was approximately Na₂O 14%, MgO 5.4%,CaO 9%, B₂O₃ 2.3%, P₂O₅ 1.5%, and SiO₂ 67.8% w/w. Testing samples weremanufactured by compression molding of multiple layers of compositematerial into an appropriate mold. Each layer was comprised of the PLDLApolymer with embedded uni-directionally aligned continuous fibers.Orientation of layers relative to longitudinal axis of implant were 0°(parallel to implant longitudinal axis), 45°, 0, −45°, 0°, in arepetitive manner according to number of layers in the implant. Eachlayer was approximately 0.18 mm thick. Three (3) implant samples wereproduced for each group.

Implant samples were weighed initially and following simulated in vitrodegradation according to a modified ASTM F1635, wherein samples wereincubated in simulated body fluid (SBF), 142 Na⁺, 5 K⁺, 1.5 Mg²⁺, 2.5Ca²⁺, 147.8 Cl⁻, 4.2 HCO₃ ⁻, 1 HPO₄ ³⁻, 0.5 SO₄ ²⁻ mol/m³, for 5 days ata temperature of 50° C., while shaking at 30 rpm. Samples were thendried in a vacuum desiccator overnight and weighed again. Materialpercentage loss was calculated as (initial weight−dried weight)/initialweight*100. Swelling ratio was calculated as (weight at the end of theincubation−dried weight)/dried weight*100.

Results

Table 4 shows the weight measurement results of different types ofreinforced composite implants produced as described above.

TABLE 4 Mean values and standard deviations of implant weightmeasurements and calculated material loss and swelling ratio (n = 3).Measurements are of the weight at the beginning of the experiment (T0),after degradation of 5 days in SBF at 50° C., 30 rpm (5 days) and afterdehydration in the desiccator overnight (dried). 5 Days Dried MaterialSwelling T0 [gr] [gr] [gr] loss (%) ratio (%) Full pin. OD  2.33 ±  2.43±  2.35 ± 0.245 4.42 6 mm. 50% w/w 0.09 0.09 0.09 Full pin. OD  2.68 ± 2.79±  2.69 ± 0.262 4.35 6 mm. 70% w/w 0.09 0.01 0.01 Hollow pin. OD 1.69 ±  1.81 ±  1.69 ± 0.262 7.57 6 mm. ID 0.01 0.01 0.01 3 mm. 50% w/wFull pin. OD 0.257 ± 0.273 ± 0.254 ± 1.24 7.456 2 mm. 50% w/w 0.01 0.010.01 Full pin. OD 0.281 ± 0.317 ± 0.274 ± 2.6 15.626 2 mm. 70% w/w 0.020.03 0.02 Hollow pin. OD 0.226 ± 0.246 ± 0.221 ± 2.085 11.347 2 mm. ID0.03 0.02 0.02 1 mm. 50% w/w Plate. 50% w/w 2.755 ± 2.870 ± 2.75 ± 0.1434.353 fiber 0.01 0.01 0.01 Plate. 70% w/w 3.158 ± 3.346 ± 3.149 ± 0.3126.237 fiber 0.3 0.3 0.25Mineral fiber concentration increase from 50% to 70%, in the 2 mm pinsand plates, increased the material loss and the swelling ratio over timeby ˜110% and more than 40% respectively. Relative degradation, asmeasured by relative material loss, seemed to be faster in cannulatedimplants vs non cannulated designs.In the 6 mm pins, mineral fiber concentration increase from 50% to 70%also caused an increase in degradation as measured by material loss %.In the 6 mm cannulated pins, the relative degradation increase couldalso be noted by the increase in swelling ratio of 74% vs the full pins.

ADDITIONAL DRAWINGS SHOWING VARIOUS EMBODIMENTS

FIG. 30 shows a continuous fiber-reinforced tape of the type that can beused to form a layer in a medical implant comprised of continuousfiber-reinforced layers. The top view (3000) shows a single strip ofcomposite tape comprising reinforcement fibers aligned in a singledirection within a bioabsorbable polymer matrix. The interspersedreinforcement fibers (3006) within the bioabsorbable polymer matrix(3008) can be seen more clearly in the close-up top view (3002) of thecontinuous-fiber reinforced composite tape. The reinforcement fibers canbe present as separate fibers or in bundles of several reinforcementfibers per bundle. The cross-sectional view of the continuous fiberreinforced tape (3004) shows the bundles of aligned reinforcement fibers(3010) embedded within the bioabsorbable polymer matrix (3012). Fiberspreferably do not breach the surface of the bioabsorbable polymermatrix.

FIG. 31 shows a cut-away, three-dimensional view of a continuousfiber-reinforced tape (200). The cut-away view shows the alignedreinforcement fibers (202) embedded within the bioabsorbable polymermatrix (204).

FIG. 32a shows a top-view of a reinforced bioabsorbable composite sheet(300) comprised of three layers of uni-directional fibers at differentangles. Each layer can optionally be comprised of continuous fiberreinforced tapes of the type depicted in FIG. 30. The expanded view(302) shows layers of uni-directional fibers at different angles withinan implant. One layer (304) aligned in the longitudinal axis, one layer(306) aligned at an angle to the right of the longitudinal axis, and onelayer (308) aligned at an angle to the left of the longitudinal axis.

FIG. 32b shows a cut-away view of a reinforced bioabsorbable compositestructure (310) comprised of three layers of uni-directional fibers atdifferent angles. One layer (312) aligned in the longitudinal axis, onelayer (314) aligned at an angle to the right of the longitudinal axis,and one layer (316) aligned at an angle to the left of the longitudinalaxis. Each layer is comprised of reinforced continuous fibers (318)embedded within bioabsorbable polymer matrix (320).

FIG. 33 shows the wall of a continuous-fiber reinforced compositemedical implant. The implant wall is comprised of two layers ofuni-directional continuous-fiber reinforced composite tape layers (402 &404) aligned at a perpendicular angle to each other. The medical implantwall additional comprises perforations (406) to allow for tissuepenetration into or through the implant.

FIG. 34 shows a bone filler cage that consists of continuous-fiberreinforced composite medical implant walls (500) that additionallycontains perforations (502) to allow tissue and cellular ingrowth intothe bone filler material (504) contained within the bone filler cage.The bone filler cage optionally includes a separate door to close thecage (506).

FIG. 35 shows a bioabsorbable cannulated screw (600) that is a medicalimplant comprised of two parts: a continuous-fiber reinforcedbioabsorbable composite cylindrical core (602) and bioabsorbable polymerthreading (604) that was subsequently molded or 3D printed on top of thecontinuous-fiber core. This is an example of a bioabsorbable medicalimplant where a significant amount or majority of the mechanicalstrength is provided by a continuous-fiber reinforced part that servesas a mechanical support or structure but where additional implantfeatures are comprised of materials that are not continuous fiberreinforced and yet can be molded or printed directly onto the fiberreinforced composite material.

It will be appreciated that various features of the invention which are,for clarity, described in the contexts of separate embodiments may alsobe provided in combination in a single embodiment. Conversely, variousfeatures of the invention which are, for brevity, described in thecontext of a single embodiment may also be provided separately or in anysuitable sub-combination. It will also be appreciated by persons skilledin the art that the present invention is not limited by what has beenparticularly shown and described hereinabove. Rather the scope of theinvention is defined only by the claims which follow.

1. A medical implant comprising a plurality of biocomposite layers, saidbiocomposite comprising a polymer and a plurality of continuousreinforcement fibers, such that each layer comprises said biocomposite,wherein said fibers are uni-directionally aligned within each layerwherein said implant is bioabsorbable and said polymer is biodegradable;wherein said fibers are continuous fibers, wherein said continuousfibers are longer than 4 mm.
 2. (canceled)
 3. The implant of claim 1,wherein said biodegradable polymer is embodied in a biodegradablecomposite comprising between 1-100, 2-40, or 4-20 reinforcing fibers ineach biocomposite layer. 4.-9. (canceled)
 10. The implant of claim 1,wherein each layer has a directional fiber orientation, and wherein saidfiber orientation alternates between adjacent layers such that eachadjacent layer is of a different angle wherein said angle differencebetween lavers is between 15 to 75 degrees, 30 to 60 degrees or 40 to 50degrees. 11.-13. (canceled)
 14. The implant of claim 1, wherein adistance between layers, as determined by a distance between a lastfiber in one layer and a first fiber in an adjacent layer, is between0-200 μm, 0-60 μm, 1-40 μm, or 2-30 μm. 15.-19. (canceled)
 20. Theimplant of claim 1, wherein said continuous fibers are longer than 8 mm,12 mm, 16 mm or 20 mm. 21.-23. (canceled)
 24. The implant of claim 1,wherein a reinforcing fiber length of at least a portion of said fibersis at least 50%, 60%, 75% of a longitudinal length of the implant; orwherein said reinforcing fiber length of a majority of said fibers is atleast 50%, 60% or 75% of said longitudinal length of the implant.25.-27. (canceled)
 28. The implant of claim 1, wherein a majority ofreinforcement fibers within the composite layer are aligned to thelongitudinal axis of the medical implant; or wherein a majority ofreinforcement fibers within the composite layer are aligned at an angleto the longitudinal axis and wherein said angle is less than 90°, lessthan 60°, or less than 45° from the longitudinal axis. 29.-32.(canceled)
 33. The implant of claim 1, wherein a diameter of said fibersis in a range of 0.1-100 μm, 1-20 μm, 4-16 μm, 6-20 μm, 10-18 μm or14-16 μm. 34.-38. (canceled)
 39. The implant of claim 1, wherein astandard deviation of fiber diameter between fibers is less than 5 μm, 3μm, or 1.5 μm. 40.-41. (canceled)
 42. The implant of claim 1, wherein adistance between adjacent reinforcing fibers within each layer is in arange of 0.5-50 μm, 1-30 μm, 1-20 μm or 1-10 μm. 43.-45. (canceled) 46.The implant of claim 1, wherein a weight percentage of fibers is in arange of 20-90% or 40%-70%; and wherein a volume percentage ofreinforcing fibers within the implant is in a range of 30-90% or40%-70%. 47.-49. (canceled)
 50. The implant of claim 1, wherein eachcomposite layer is of thickness 0.05 mm-0.5 mm, 0.15-0.35 mm, or; andwherein each composite layer is of width 2-30 mm. 51.-53. (canceled) 54.The implant of claim 1, wherein a density of the biocomposite is between1 to 2 g/ml, 1.2 to 1.9 g/ml, or 1.4 to 1.8 g/ml. 55.-56. (canceled) 57.The implant of claim 1 wherein the medical implant comprises between2-20, 2-10, or 2-6 composite layers. 58.-74. (canceled)
 75. The implantof claim 1 wherein fibers are present as part of fiber bundles.
 76. Theimplant of claim 1 wherein fiber bundles are present in a single,non-overlapping layer within each composite layer. 77.-79. (canceled)80. The implant of claim 1, wherein said biodegradable polymer comprisesa homopolymer or a copolymer; wherein said copolymer comprises a randomcopolymer, block copolymer, or graft copolymer; wherein said polymercomprises a linear polymer, a branched polymer, or a dendrimer, ofnatural or synthetic origin; and wherein said polymer comprisescomprises lactide, glycolide, caprolactone, valerolactone, carbonates(e.g., trimethylene carbonate, tetramethylene carbonate, and the like),dioxanones (e.g., 1,4-dioxanone), δ-valerolactone, 1,dioxepanones) e.g.,1,4-dioxepan-2-one and 1,5-dioxepan-2-one), ethylene glycol, ethyleneoxide, esteramides, γ-ydroxyvalerate, β-hydroxypropionate, alpha-hydroxyacid, hydroxybuterates, poly (ortho esters), hydroxy alkanoates,tyrosine carbonates, polyimide carbonates, polyimino carbonates such aspoly (bisphenol A-iminocarbonate) and poly (hydroquinoneiminocarbonate,(polyurethanes, polyanhydrides, polymer drugs (e.g., polydiflunisol,polyaspirin, and protein therapeutics), sugars; starch, cellulose andcellulose derivatives, polysaccharides, collagen, chitosan, fibrin,hyaluronic acid, polypeptides, proteins, poly (amino acids),polylactides (PLA), poly-L-lactide (PLLA), poly-DL-lactide (PDLLA);polyglycolide (PGA); copolymers of glycolide, glycolide/trimethylenecarbonate copolymers (PGA/TMC); other copolymers of PLA, such aslactide/tetra methylglycolide copolymers, lactide/trimethylene carbonatecopolymers, lactide/d-valerolactone copolymers, lactide/ε-caprolactonecopolymers, L-lactide/DL-lactide copolymers, glycolide/L-lactidecopolymers (PGA/PLLA), polylactide-co-glycolide; terpolymers of PLA,such as lactide/glycolide/trimethylene carbonate terpolymers,lactide/glycolide/ε-caprolactone terpolymers, PLA/polyethylene oxidecopolymers; polydepsipeptides; unsymmetrically-3,6-substitutedpoly-1,4-dioxane-2,5-diones; polyhydroxyalkanoates; such aspolyhydroxybutyrates (PHB); PHB/b-hydroxyvalerate copolymers (PHB/PHV);poly-b-hydroxypropionate (PHPA); poly-p-dioxanone (PDS);poly-d-valerolactone-poly-ε-capralactone,poly(ε-caprolactone-DL-lactide) copolymers; methylmethacrylate-N-vinylpyrrolidone copolymers; polyesteramides; polyesters of oxalic acid;polydihydropyrans; polyalkyl-2-cyanoacrylates; polyurethanes (PU);polyvinylalcohol (PVA); polypeptides; poly-b-malic acid (PMLA):poly-b-alkanbic acids; polycarbonates; polyorthoesters; polyphosphates;poly(ester anhydrides); and mixtures thereof; and derivatives,copolymers and mixtures thereof.
 81. The implant of claim 80, whereinsaid polymer is selected from the group consisting of PLLA, PDLA, PGA,PLGA, PCL, PLLA-PCL and a combination thereof.
 82. The implant of claim81, wherein said PLLA is used in said polymer matrix and said matrixcomprises at least 30%, 50%, or 70% PLLA. 83.-84. (canceled)
 85. Theimplant of claim 81, wherein said PDLA is used in said polymer matrixand said matrix comprises at least at least 5%, 10%, or 20% PDLA.86.-87. (canceled)
 88. The implant of claim 1 wherein said fibercomprises a silica-based mineral compound.
 89. The implant of claim 88,wherein said silica-based mineral compound has at least one oxidecomposition in at least one of the following mol. % ranges: Na₂O:11.0-19.0 mol. % CaO: 9.0-14.0 mol. % MgO: 1.5-8.0 mol. % B₂O₃: 0.5-3.0mol. % Al₂O₃: 0-0.8 mol. % P₂O₃: 0.1-0.8 mol. %
 90. The implant of claim89, wherein said silica-based mineral compound has at least one oxidecomposition in at least one of the following mol. % ranges: Na₂O:12.0-13.0 mol. % CaO: 9.0-10.0 mol. % MgO: 7.0-8.0 mol. % B₂O₃: 1.4-2.0mol. % P₂O₃: 0.5-0.8 mol. % SiO₂: 68-70 mol. %. 91.-115. (canceled) 116.The implant of claim 1, wherein the fibers are arranged in bundleswithin each layer.
 117. The implant of claim 1, wherein the layers arearranged in circular bundles.
 118. A method of treatment for anorthopedic application in a subject in need of treatment thereof,comprising implanting to the medical implant of claim
 1. 119.-120.(canceled)